SCOR research over the past several years has identified changes in the myofibroblast population as an important component of the interstitial fibrosis that develops in humans and animals. The purpose of this research is to address two cardinal questions: 1) what causes the myofibroblast to appear; and 2) what does the myofibroblast do? In vivo experiments will examine the appearance of these cells early in the time course of bleomycin- induced fibrosis in terms of replication, location and relationship to key matrix components we hypothesize are involved in their genesis, specifically fibronectin and type III collagen. These cells in turn will be examined in terms of their potential output of the same matrix components. In vitro studies will involve lung fibroblasts cultured on planar surfaces and in hydrated collagen gels using methods that will allow them to be stressed mechanically. Again, the relationship between myofibroblast phenotype and specific matrix elements will be examined. Experiments also will be conducted to define patterns and causative factors of (myo) fibroblast migration, as well as to ask if myofibroblast filament bundles are responsible for generating stress (contractile force) or rather are a response to stress. Thus, the research will attack the fundamental cell biology of a cell commonly thought to be involved in both physiologic and pathologic tissue remodeling and which, in particular, appears to play a critical role in remodeling lung.